Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral
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Open Access
Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART Rose C. Kitawi1,2, Carol W. Hunja1,3, Rashid Aman1,4,6, Bernhards R. Ogutu1,5,6, Anne W. T. Muigai2, Gilbert O. Kokwaro5 and Washingtone Ochieng1,5,6,7*
Abstract Background: HIV-1 is highly variable genetically and at protein level, a property it uses to subvert antiviral immunity and treatment. The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes. Methods: A total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI’s Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. Viral tropism was assessed using Geno2Pheno (G2P), WebPSSM and Phenoseq platforms as well as using Raymond’s and Esbjörnsson’s rules. Chi square test was used to determine independent variables association and ANOVA applied on scale variables. Results: At respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. Raymond’s rule (p = 0.024) and WebPSSM (p = 0.05), but not Phenoseq or Esbjörnsson showed significant associations between subtype and tropism. Relative to other platforms used, Raymond’s and Esbjörnsson’s rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. The mean glycosylation density differed significantly between subtypes at positions, N277 (p = 0.034), N296 (p = 0.036), N302 (p = 0.034) and N366 (p = 0.004), with HIV-1D most heavily glycosylated of the subtypes. R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011). (Continued on next page)
* Correspondence: [email protected]; [email protected] 1 Center for Research in Therapeutic Sciences, Strathmore University, P.O. Box 59857-00200, Nairobi, Kenya 5 Institute of Healthcare Management, Strathmore University, P.O. Box 59857-00200, Nairobi, Kenya Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),
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